Lymphocyte mediated cell killing is thought to be the principal process responsible for the immunological rejection of grafts and tumors, yet the basic mechanism for this killing is unknown. The present evidence suggests that lymphocyte surface molecules recognize the target cell, leading to a specific adherence between attacker and target. We have developed a model for this phase of the killing process for antibody dependent lymphocyte killing in which lymphocytes interact with plastic surfaces coated by antigen antibody complexes. A dramatic change in cell shape follows this binding, and we plan to define the metabolic and functional consequences of this; in particular, we plan to test the hypothesis that this shape change is necessary for killing. We furthermore will attempt to develop a parallel model for immune T cell killing. The mechanism of target cell destruction following attacker cell adherence has been studied using antibody coated lipid bilayers; we have shown that the membrane electrical conductance increased by several orders of magnitude under conditions simulating target cell killing. We plan to define the ionic selectivity of this conductance increase, and also to attempt to model immune T cell killing using antigen coated membranes.